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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

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World Journal of Gastroenterology 2015年第11期21卷 3291-3299页

作者： Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima kunitaka fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Department of Gastroenterology and Clinical Research Center National Hospital Organization Kyushu Medical Center Health Care Center Fukuoka University Product Research Department Chugai Pharmaceutical Co.Ltd. Department of Medicine and Bioregulatory Science Kyushu University

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C ***:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively *** biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for *** a control,normal liver tissue was obtained from 18 living donors of liver *** hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass ***:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in ***,iron administration suppresses HCV replication in ***,the association between HCV infection and iron metabolism remains *** with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and *** the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and *** of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected ***2 and hemojuvelin expression was significantly lower in the SVR than non-SVR *** infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in ***:Decrea

关键词： Chronic hepatitis C Iron-metabolism Hepcidin Ferro

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Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2013年第3期4卷 54-60页

作者： Tatsuya Fujino Yoko Aoyagi Mariko Takahashi Ryoko Yada Naoko Yamamoto Yuki Ohishi Akihiko Nishiura Motoyuki Kohjima Tsuyoshi Yoshimoto kunitaka fukuizumi Manabu Nakashima Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Munechika Enjoji Laboratory for Clinical Investigation National Hospital Organization Nagasaki Medical CenterOhmuraNagasaki 856-8562Japan Clinical Research Institute National Hospital Organization Kyushu Medical CenterFukuoka 814-0180Japan Faculty of Pharmaceutical Sciences Fukuoka UniversityFukuoka 814-0180Japan Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 814-0180Japan

AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) ***:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based *** in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA ***:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA ***,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not ***:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV ***,CC genotype was not inferior to CA/AA genotype for SVR *** full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.

关键词： Chronic hepatitis C Interleukin 28B Inosine triphosphatase Peginterferon Ribavirin

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